Thermal shielding to optimize lyophilization process for pre-filled syringes or vials

ABSTRACT

A device for supporting at least one vessel containing a target material to be lyophilized generally includes a support panel, a central region, a perimeter region, a thermal shield, and at least one shielding cavity. The support panel has a support surface. The central region is defined by the support panel for supporting the at least one vessel. The perimeter region is also defined by the support panel and surrounding the central region. The thermal shield is positioned about the perimeter region and extends transverse to the support surface of the support panel such that the thermal shield and the support panel define a storage space for accommodating the at least one vessel. The at least one shielding cavity is defined by the thermal shield and contains a shielding material during a lyophilization process. The shielding material is distinct from the target material.

FIELD OF THE DISCLOSURE

The present disclosure is generally directed to devices, systems, andmethods for conducting a lyophilization process on a target materialand, more particularly, to devices, systems, and methods for obtaining auniform temperature distribution of the target material while undergoingthe lyophilization process.

BACKGROUND

Lyophilization, which can also be referred to as freeze-drying, is adehydration process typically used to preserve a perishable targetmaterial or make the target material more convenient for transport.Lyophilization works by freezing the target material and then reducingthe surrounding pressure and adding sufficient heat to allow the frozenwater in the target material to sublimate directly from a solid to agas. The gas is then removed from the target material to completedehydration.

Conventional lyophilization processes are carried out with freeze-dryingmachines. A typical freeze-drying machine includes a lyophilizationchamber, within which the target material is disposed during thelyophilization process. The lyophilization chamber generally includes abox-shaped structure having one or more sidewalls, a top wall, and abottom wall. Moreover, the chamber can include one or more shelves orracks, for example, for storing the target material.

SUMMARY

One aspect of the present disclosure provides a device for supporting atleast one vessel containing a target material to be lyophilized. Thedevice includes a support panel, a central region, a perimeter region, athermal shield, and at least one shielding cavity. The support panel hasa support surface. The central region is defined by the support panelfor supporting the at least one vessel. The perimeter region is alsodefined by the support panel and surrounding the central region. Thethermal shield is positioned about the perimeter region and extendstransverse to the support surface of the support panel such that thethermal shield and the support panel define a storage space foraccommodating the at least one vessel. The at least one shielding cavityis defined by the thermal shield and contains a shielding materialduring a lyophilization process. The shielding material is distinct fromthe target material.

The thermal shield can optionally include an inner wall portion and anouter wall portion. The inner wall portion surrounds the central region.The outer wall portion surrounds the inner wall portion and is spacedfrom the inner wall portion to define the at least one shielding cavity.

The at least one shielding cavity defined between the inner and outerwall portions of the thermal shield can optionally include an elongatedchannel surrounding the central region of the support panel and forcontaining the shielding material.

The device can further optionally include an elongated opening definedby the elongated channel for enabling at least one component of theshielding material to exhaust from the elongated channel during thelyophilization process.

The device can further optionally include a cap enclosing the elongatedchannel. The cap can define a plurality of apertures for controlling arate at which the shielding material exhausts from the channel duringthe lyophilization process.

The thermal shield can optionally include a plurality of shieldingrepositories arranged side-by-side about the perimeter region of thesupport panel and surrounding the central region. Each of the pluralityof repositories can define a shielding cavity containing the shieldingmaterial during the lyophilization process.

Each of the shielding repositories can optionally comprise a syringetube.

Another aspect of the present disclosure includes a system forlyophilizing target material stored within at least one vessel. Thesystem generally includes a freeze-drying machine and the device asdescribed herein, such as one according to any of the foregoing aspects.The freeze-drying machine includes a chamber having chamber walls, andthe device is removably supported within the chamber. So configured, thethermal shield of the device substantially inhibits transmission of orabsorbs thermal radiation emitted by the chamber walls of the freezedrying machine while the target material is being lyophilized, therebyfacilitating a uniform temperature distribution amongst the targetmaterial stored in the at least one vessel.

A further aspect of the present disclosure includes a method oflyophilizing a target material stored in at least one vessel. The methodgenerally includes at least partially filling at least one shieldingcavity with a shielding material that includes at least one componentthat is different than at least one component of the target material.The at least one shielding cavity can be arranged to surround the atleast one vessel. The method further includes loading the at least onevessel and the at least one shielding cavity into a lyophilizationchamber of a freeze drying machine. The lyophilization chamber can havesidewalls and can be arranged and configured to support the at least onevessel and the at least one shielding cavity. The method furtherincludes lyophilizing the target material stored in the at least onevessel. The method still further includes inhibiting transmission of orabsorbing thermal radiation emitted from the sidewalls of thelyophilization chamber to prevent it from reaching the at least onevessel, thereby minimizing variations in temperature amongst the targetmaterial stored in the at least one vessel.

The method can further optionally include loading the at least onevessel onto a central region of a support panel.

The method can further optionally include with a shielding material atleast partially filling at least one elongated channel that is adaptedto surround the at least one vessel.

The method can further optionally include at least partially filling aplurality of repositories arranged side-by-side and adapted to surroundthe at least one vessel with a shielding material.

Inhibiting the thermal radiation can optionally include cooling aperimeter region within the lyophilization chamber, the perimeter regionsurrounding the at least one vessel and being disposed between the atleast one vessel and the sidewalls of the lyophilization chamberadjacent to the shielding material.

Cooling the perimeter region can optionally include lyophilizing atleast a portion of the shielding material stored in the at least oneshielding cavity generally simultaneously with lyophilizing the targetmaterial stored in the at least one vessel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a system for lyophilizing a targetmaterial constructed in accordance with the principles of the presentdisclosure and including a freeze-drying machine accommodating a devicesupporting at least one vessel containing the target material;

FIG. 2 is a cross-sectional view taken through line II-II of FIG. 1 andincluding one embodiment of a device for supporting at least one vesselof target material in accordance with the principles of the presentdisclosure;

FIG. 2A is a partial cross-sectional side view taken through lineIIA-IIA of FIG. 2;

FIG. 3 is across-sectional view taken through line II-II of FIG. 1 andincluding an alternative embodiment of a device for supporting at leastone vessel of target material in accordance with the principles of thepresent disclosure; and

FIG. 4 is a cross-sectional view taken through line II-II of FIG. 1 andincluding another alternative embodiment of a device for supporting atleast one vessel of target material in accordance with the principles ofthe present disclosure;

FIG. 5 is a plan view of a device supporting a plurality of vesselscontaining a target material and indicating the position of a pluralityof temperature probes utilized during a test lyophilization process;

FIG. 6 is a graphical representation of the temperatures sensed by theplurality of temperature probes of FIG. 5 during a cooling step of thetest lyophilization process conducted without the use of a thermalshield of the present disclosure;

FIG. 7 is a graphical representation of the temperatures sensed by theplurality of temperature probes of FIG. 5 during a cooling step of atest lyophilization process conducted with the use of a thermal shieldof the present disclosure;

FIG. 8 is a graphical representation of the temperatures sensed by theplurality of temperature probes of FIG. 5 during a drying step of a testlyophilization process conducted without the use of a thermal shield ofthe present disclosure;

FIG. 9 is a graphical representation of the temperatures sensed by theplurality of temperature probes of FIG. 5 during a drying step of a testlyophilization process conducted with the use of a thermal shield of thepresent disclosure; and

FIG. 10 is a plan view of a device supporting a plurality of vesselscontaining a target material and illustrating a thermal shield includingtwo interlocked pieces.

DETAILED DESCRIPTION

FIG. 1 depicts a system 10 for lyophilizing a target material includinga freeze-drying machine 12 accommodating a device 100 supporting aplurality of vessels 14 that contain the target material 15 (shown inFIG. 2A). In the present embodiment, the plurality of vessels 14 caninclude syringe tubes, vials, beakers, or any other material-containingdevice. In other embodiments, the device 100 can be arranged andconfigured to contain a single vessel 14 as opposed to a plurality ofvessels 14. In yet another alternative embodiment, the device 100 can bearranged to directly contain the target material 15 without the need forany intervening vessel(s). The freeze-drying machine 12 defines alyophilization chamber 16 that is selectively openable/closeable with adoor (not shown), for example. The device 100 is disposed within thelyophilization chamber 16 such that the target material 15 carriedwithin the vessels 14 can be lyophilized upon activation of thefreeze-drying machine 12.

To lyophilize the target material 15, the freeze-drying machine 12 firstperform a cooling step and reduces the temperature within thelyophilization chamber 16 to a temperature below the freezing point ofat least one component of the target material 15, for example in therange of approximately negative twenty degrees Celsius (−20° C.) toapproximately negative seventy degrees Celsius (−70° C.). Then, thefreeze-drying machine 12 performs a drying step, whereby the ambientpressure of the lyophilization chamber 16 is reduced with a vacuum pump(not shown), for example, to a pressure that is substantially less thanatmospheric pressure, such as a pressure in the range of approximately1.33 Pa (0.01 Torr) to approximately 133 Pa (1 Torr). With the ambientpressure reduced, a sufficient amount of heat can be added to thelyophilization chamber 16 to sublimate the frozen water in the targetmaterial 15 from a solid to a gas. The gaseous water is then removedfrom the target material 15 and collected on a condenser plate (notshown), for example, such that the target 15 remains “freeze-dried.” Thepressure within the lyophilization chamber 16 can then be increased orreturned to the ambient pressure outside of the lyophilization chamber16, and the vessels 14 can be removed from the freeze-drying machine 12for packaging or further processing of the target material 15.

FIGS. 2 and 2A depict one embodiment of a device 100 for supporting theplurality of vessels 14 disposed within the lyophilization chamber 16 ofthe freeze-drying machine 12 of FIG. 1. As illustrated in FIG. 2, thelyophilization chamber 16 is defined between front and rear walls 18 a,18 c and opposing left and right side walls 18 d, 18 b. The front wall18 a may be embodied by a door or other movable panel, for example, anddefines the front of the freeze-drying machine 12, through which thevarious items are loaded into the lyophilization chamber 16. Moreover,as shown in FIG. 1, the lyophilization chamber 16 includes a bottom wall20 located beneath the device 100 and a top wall 22 located above thedevice 100.

With continued reference to FIGS. 1, 2, and 2A, the device 100 includesa support panel 102, which can constitute a shelf or tray supportedwithin the lyophilization chamber 16, and a thermal shield 108. Thesupport panel 102 is a generally flat rectangular member having acentral region 104 and a perimeter region 106. The top surface of thesupport panel 102 defines a support surface 102 a. The perimeter region106 of the support panel 102 surrounds, e.g., circumscribes, the centralregion 104. The central region 104 supports the plurality of vessels 14and, in some embodiments, can include a plurality of recesses or otherfeatures for maintaining the position and/or alignment of the vessels14.

The thermal shield 108 is positioned on the perimeter region 106 of thesupport panel 102 and defines at least one shielding cavity 110. Asillustrated in FIG. 2A, the thermal shield 108 includes a bottom wallportion 101, an inner wall portion 112, and an outer wall portion 114.The bottom wall portion 101 is supported directly on the support surface102 a of the support panel 102 and the inner and outer wall portions112, 114 extend generally parallel to each other and transverse to thebottom wall portion 101 and the support surface 102 a of the supportpanel 102. In the present embodiment, the inner and outer wall portions112, 114 extend perpendicularly from the bottom wall portion 101 of thethermal shield 108 and the support surface 102 a of the support panel102, as is illustrated in FIGS. 1 and 2A. The inner wall portion 112surrounds, e.g., circumscribes, the central region 104 of the supportpanel 102. So configured, the thermal shield 108 and the support panel102 define a three-dimensional storage space 111 (shown in FIG. 1)accommodating the plurality of vessels 14 of the target material 15. Theouter wall portion 114 surrounds, e.g., circumscribes, the inner wallportion 112 and is spaced from the inner wall portion 112 to define theat least one shielding cavity 110. The at least one shielding cavity 110is adapted to contain a shielding material 119 (shown in FIG. 2A) thatis distinct from the target material 15.

In the embodiment of the device 100 depicted in FIG. 2, the thermalshield 108 is constructed of two separable portions including a rearportion 108 a and a front portion 108 b. The rear portion 108 a includesa unitary or one-piece structure having first through third legs 109a-109 c arranged in a U-shape such that the first leg 109 a is disposednearest the right side wall 18 b of the lyophilization chamber 16, thesecond leg 109 b is disposed nearest the rear wall 18 c of thelyophilization chamber 16, and the third leg 109 c is disposed nearestthe front wall 18 a of the lyophilization chamber 16. Furthermore, asillustrated, the front portion 108 b of the present embodiment of thethermal shield 108 includes a unitary or one-piece structure including asingle leg 109 d positioned adjacent the open end of the U-shaped rearportion 108 a of the thermal shield 108 such that the thermal shield 108as a whole completely surrounds, i.e., circumscribes, the central region104 of the support panel 102. As mentioned, the rear and front portions108 a, 108 b of the thermal shield 108 are separable. So configured, therear and front portions 108 a, 108 b can facilitate loading the thermalshield 108 and the plurality of vessels 14 into the lyophilizationchamber 16. For example, to prepare the lyophilization process, thesupport panel 102 can first be loaded into the lyophilization chamber 16through an opening (shown in FIG. 1) in the front of the freeze-dryingmachine 12. Then, the rear portion 108 a of the thermal shield 108including the first though third legs 109 a-109 c can be loaded onto thesupport panel 102 through the opening in the front of the freeze-dryingmachine 12. Then, the plurality of vessels 14 containing target material15 can be loaded onto the central region 104 of the support panel 102through the opening in the front of the freeze-drying machine 12.Finally, the front portion 108 b of the thermal shield 108 can be loadedinto the lyophilization chamber 16 and on the support panel 102 adjacentthe rear portion 108 a, as depicted in FIG. 2.

In the embodiment illustrated in FIG. 2, the front portion 108 b of thethermal shield 108 abuts up against ends of the first and third legs 109a, 109 c of the rear portion 108 a of the thermal shield 108. In analternative embodiment, which is illustrated in FIG. 10, the rear andfront portions 108 a, 108 b of the thermal shield 108 can interlock. Forexample, as illustrated in FIG. 10, the ends of the first and third legs109 a, 109 c of the rear portion 108 a of the thermal shield 108 caninclude recesses 181 and the leg 109 d of the front portion 108 b caninclude tongues 183 that are adapted to be removably disposed within therecesses 181. This interlocking connection can assist in aligning therear and front portions 108 a, 108 b of the thermal shield 108.

Referring back to FIG. 2, with the thermal shield 108 configured toinclude the rear and front portions 108 a, 108 b, as described, theshielding cavity 110 is divided into two shielding cavity portionsincluding U-shaped a rear shielding cavity portion 110 a defined by therear portion 108 a of the thermal shield 108 and a straight frontshielding cavity portion 110 b defined by the front portion 108 b of thethermal shield 1108. Each shielding cavity portion 110 a, 110 b, andtherefore, the shielding cavity 110 as a whole can be described asincluding an elongated channel 120 defining an elongated opening 121(shown in FIG. 2A) at a location opposite the inner and outer wallportions 112, 114 from the bottom wall portion 101. The elongatedopening 121 opens the elongated channel 120 to the ambient atmosphere ofthe lyophilization chamber 16 when the device 100 is disposed in thefreeze-drying machine 12.

The elongated channel 120 surrounds, e.g., circumscribes, both the innerwall portion 112 of the thermal shield 108 and the central region 104 ofthe support panel 102. As such, the elongated channel 120 alsosurrounds, e.g., circumscribes, the plurality of vessels 14 supported onthe support panel 102.

In the embodiment depicted in FIG. 2A, each of the vessels 14 includes aconventional syringe tube 130 having a reduced-diameter tip portion 132and a base portion 134. The tip portion 132 of each syringe tube 130 caninclude a sealed orifice (not shown), for example, that is adapted toreceive a hypodermic need for delivering a liquid material out of thesyringe tube 130. In the disclosed embodiment, the tip portion 132 ofeach syringe tube 130 is supported on the support surface 120 a withinthe central region 104 of the support panel 120. The base portion 134 ofthe syringe tube 130 defines a circular opening 136 that is adapted toreceive a syringe plunger (not shown) in a conventional manner. As shownin FIG. 2A, syringe plungers are not included within the syringe tubes130 during the lyophilization process such that the target material 15is in direct communication with the ambient atmosphere of thelyophilization chamber 16 via the openings 136.

With this arrangement of the device 100, the thermal shield 108 isdisposed between, e.g., separates, the front, rear, and side walls 18a-18 d of the lyophilization chamber 16 and the plurality of vessels 14,as depicted in FIGS. 2 and 2A. So configured, the thermal shield 108 caninsulate the vessels 14 by substantially inhibiting and/or preventingthermal radiation that is emitted by the walls 18 a-18 d of thelyophilization chamber 16 front reaching the vessels 14 while the targetmaterial 15 is being lyophilized, e.g., by blocking transmission and/orby absorbing the energy. This shielding can help ensure that thetemperature of the target material 15 across the plurality of vessels 14is generally uniform at any given time during the lyophilizationprocess, which provides uniformity and quality assurance of thedehydrated target material 15.

For example, as depicted in FIG. 2A, the shielding cavity 110 of thethermal shield 108, which in the present embodiment includes theelongated channel 120, is adapted to contain a shielding material 119.As such, the shielding material 119 is disposed between, e.g.,separates, the walls 18 a-18 d of the lyophilization chamber 16 and thevessels 14 containing the target material 15. The shielding material 119can, for example, include a liquid, wherein at least one component ofthe liquid is water. The shielding material 119 can optionally includeonly water. In other embodiments, the shielding material 119 couldforeseeably include other liquids, or even gases, or solids, so long asthe selected shielding material 119 serves one or more principles of thedisclosure. Preferably, the shielding material has a phase changeinterface (e.g., sublimation curve or melting curve) within thetemperature and pressure ranges employed in lyophilization of the targetmaterial 15. Preferably, the shielding material 119 is a liquid at roomtemperature which can be sublimated during lyophilization of the targetmaterial 15.

As discussed above, during lyophilization, the ambient temperature ofthe lyophilization chamber 16 can be reduced during a cooling step to atemperature in the range of approximately negative twenty degreesCelsius (−20° C.) to approximately negative seventy degrees Celsius(−70° C.), for example. In this temperature range, the shieldingmaterial 119 and the target material 15 freeze solid. Then, during adrying step, the ambient pressure in the lyophilization chamber 16 isreduced and sufficient heat can be added to sublimate the targetmaterial 15. Sublimation generally includes transitioning any solidfrozen water that is in the target material 15 directly to the gaseousphase. The water in the gaseous phase is then exhausted from the targetmaterial 15 through the circular openings 136 of the vessels 14, asindicated with arrows G1 in FIG. 2A, for example.

During this lyophilization process, the arrangement and configuration ofthe thermal shield 108 of the present embodiment serves as a physicalbarrier, e.g., insulator, that substantially inhibits or preventsthermal radiation Q emitted from the walls 18 a-18 d from reaching thetarget material 15. In the absence of the thermal shield 108, thethermal radiation Q can raise the temperature of the target material 15stored in some of the vessels 14. The target material 15 stored in thevessels 14 nearest the walls 18 a-18 d can experience the greatestimpact from the radiation. As such, the target material 15 stored withinthese outer-most vessels 14 would otherwise lyophilize at a differentrate than the target material 15 stored in the more interior vessels 14.Such varying rates of lyophilization can result in end product ofvarying quality.

In addition to providing a physical barrier, e.g., insulator, thethermal shield of the present embodiment can provide a sublimationcooling effect to combat the influence of thermal radiation on thetarget material 15 by absorbing such energy at steady-state temperaturevia phase change of the shielding material 119. For example, when thetarget material 15 is lyophilized, as described above, any water in theshielding material 119 stored in the thermal shield 108 of the presentembodiment at least partly sublimates. That is, as the pressure in thelyophilization chamber 16 is reduced and heat is added, any water withinthe shielding material 119 transitions from a solid, e.g., frozenmaterial, to a gas and the gas exhausts from the elongated channel 120through the elongated opening 121 in the thermal shield 108, asindicated with arrows G2 in FIG. 2A.

During this phase change, the shielding material 119 will absorb thermalradiation Q emitted by the chamber side walls, which in the presentembodiment includes at least the walls 18 a-18 d. For example, asmentioned above, lyophilizing the target material 15 can generallyinclude a cooling step followed by a drying step. During the dryingstep, the ambient pressure is reduced and sufficient heat can be addedsuch that components of both the target material 15 and the shieldingmaterial 119 transition directly from a solid to a gas. With thepressure maintained in this reduced state, any additional heat added tothe shielding material 119 will increase the rate of sublimation.Accordingly, when the thermal radiation Q emitted by the walls 18 a-18 dof the lyophilization chamber 16 acts on the shielding material 119, thesublimation rate of the shielding material 119 increases, while theactual temperature of the shielding material 119 stays the same. Assuch, it can be said that the shielding material 119 absorbs any excessenergy emitted by the walls 18 a-18 d, for example, such that all of thetarget material 15 stored in the vessels 14 can be maintained at auniform temperature. The foregoing configuration can be described asproviding a sublimation cooling effect that advantageously substantiallyinhibits or prevents thermal radiation Q emitted by the walls 18 a-18 dof the lyophilization chamber 16 from reaching the target material 15stored in the vessels 14.

While the foregoing embodiment of the device 100 has been described asbeing configured to support a plurality of vessels 14 that constitutesyringe tubes 130 arranged in a “tip-down” orientation, i.e., with theirtip portions 132 engaging the support panel 102, alternative embodimentsof the device 100 can include the syringe tubes 130 arranged in a“tip-up” orientation, i.e., with their base portions 134 engaging thesupport panel 102. In such an embodiment, the syringe tubes 130 canreceive plungers to seal the circular openings 136 at the base portions134 and the gaseous water can exit from an opening in the tip portions132 that is adapted to receive a hypodermic needle. Moreover, asmentioned above, still further alternative embodiments could include atleast some of the vessels 14 being embodied by vials, beakers, orgenerally any other structure capable of storing the target material 15.

While the thermal shield 108 of the device 100 has thus far beendisclosed as including an elongated channel 120 having an elongatedopening 121 in direct communication with the lyophilization chamber 16for exhausting the sublimated water of the shielding material 119,alternative embodiments could be constructed differently. For example,FIG. 3 depicts a modified version of the device 100 depicted in FIGS. 2and 2A further including a cap 140 at least partly enclosing theelongated channel 120 of the thermal shield 108. The cap 140 can controlthe flow of the sublimated shielding material 119 as it exhausts fromthe channel 120 by restricting the ability of the gas to exit thechannel 120. But for the inclusion of the cap 140, the modified versionof the device 100 depicted in FIG. 3 is otherwise identical to thedevice 100 described above with reference to FIGS. 2 and 2A. As such,the thermal shield 108 includes rear and front portions 108 a, 108 b,and the cap 140 includes corresponding rear and front cap portions 140a, 140 b.

As shown, the cap 140 includes an elongated member in the same shape asthe channel 120 and defines a plurality of apertures 142, through whichthe sublimated shielding material 119 is able to exhaust. Only oneaperture 142 is identified by reference numeral in FIG. 3 for the sakeof clarity. The disclosed embodiment of the cap 140, which includes boththe rear cap portion 140 a and the front portion 140 b, includes sixteenapertures (16) of common diameter generally equally spaced along thelength of the cap 140. Alternative embodiments, however, can includegenerally any number of apertures, any size of apertures, or any mixtureof sizes and/or spacing of apertures. The combined area of the pluralityof apertures 142 of the cap 140 is substantially smaller than theoverall area of the elongated opening 121 of the thermal shield 108described above with reference to FIGS. 2 and 2A. As such, the pluralityof apertures 142 can control, e.g., decrease and/or increase, a rate atwhich the sublimated shielding material 119 can exhaust out of thechannel 120 relative to the elongated opening 121. By controlling therate at which the sublimated shielding material 119 exhausts from theelongated channel 120, the degree to which the sublimation coolingeffect cools the thermal shield 108 and perimeter region of thelyophilization chamber 16, thereby insulating the target material 15 canbe controlled.

As depicted, the cap 140 of the present embodiment extends the entirelength of the channel 120 and is removably disposed on top surfaces ofthe inner and outer wall portions 112, 114 of the thermal shield 108.The cap 140 optionally can be fixed to the inner and outer wall portions112, 114 of the thermal shield 108 with fasteners such as screws, bolts,an adhesive, a weld bead, etc. Each cap portion 140 a, 140 b can beconstructed of a single piece of material or can be constructed of aplurality of pieces of material. In the alternative, each cap portion140 a, 140 b can be constructed integrally, e.g., as a single piece,with the rear and front portions 108 a, 108 b of the thermal shield 108,for example.

While the foregoing embodiments of the device 100 include rear and frontcavity portions 110 a, 110 b that each define a single contiguouscavity, e.g., a channel, for containing shielding material 119,alternative embodiments of the cavity portions 110 a, 110 b can eachforeseeably include a plurality of distinct cavities, either bridged bya structural material to create a unitary structure comprising multiplesuch cavities, or connected by passageways that enable the shieldingmaterial 119 to flow between the cavities.

Furthermore, while the foregoing embodiments of the device 100 have beendescribed as including thermal shields 108 that are constructed of innerand outer wall portions 112, 114 defining two cavity portions 110 a, 110b that collectively surround, e.g., circumscribe, the target material15, alternative embodiments of the device can include a thermal shieldincluding any number of separate shielding cavities.

For example, FIG. 4 depicts one alternative embodiment of a device 200constructed in accordance with the principles of the present disclosureand disposed within a lyophilization chamber 16 of the freeze-dryingmachine 12 of FIG. 1, for example. As with the device 100 describedabove, the device 200 includes a support panel 202 defining a supportsurface 202 a and including a central region 204 and a perimeter region206. These aspects are generally identical to the corresponding aspectsof the device 100 described above, and therefore, the specific detailswill not be repeated. The central region 204 supports a plurality ofvessels 14 storing target material 15 that has been lyophilized or is tobe lyophilized. FIG. 4 only identifies a single vessel 14 by referencenumeral for the sake of clarity.

The device 200 further includes a thermal shield 208 positioned aboutthe perimeter region 206 of the support panel 202 and defining aplurality of shielding cavities 210, only one of which is identified byreference numeral. For the sake of description only, FIG. 4 illustratesa pair of dashed lines containing the thermal shield 208 of the device200. The thermal shield 208 generally includes a plurality of shieldingrepositories 212 arranged side-by-side on the perimeter region 206 ofthe support panel 202. As such, the plurality of shielding repositories212 surround, e.g., circumscribe, the central region 204 of the supportpanel 202 and the plurality of vessels 14 storing the target material15.

In one embodiment, each of the plurality of repositories 212 can includea tube 230. The tubes 230 can include cylindrical tubes having circularopenings 228. The tubes 230 can include shielding material 119, asdescribed herein. For the sake of description, the cylindrical tubes canalso be described as including inner and outer wall portions 222, 224extending generally transverse to, e.g., perpendicular to, the supportsurface 202 a of the support panel 202. So configured, it can be saidthat the tubes 230 of the thermal shield 20 and the support panel 202 ofthe present embodiment of the device 200 depicted in FIG. 4 define athree-dimensional storage space 211 accommodating the plurality ofvessels 14. The inner wall portion 222 of each of the plurality ofshielding repositories 212 is disposed facing the plurality of vessels14, and the outer wall portion 224 of each of the plurality of shieldingrepositories 212 is disposed facing one of the walls 18 a-18 a of thelyophilization chamber 16.

In the embodiment of the device 200 depicted in FIG. 4, the cylindricalshielding repositories 212 define the shielding cavities 210 asincluding cylindrical cavities 226. Each cylindrical cavity 226 is opento the ambient atmosphere of the lyophilization chamber 16 via thecircular opening 228 of the respective shielding repository 212 when thedevice 200 is disposed in the freeze-drying machine 12.

With the device 200 configured as described, the thermal shield 208functions similar to the thermal shields 108 described above withreference to FIGS. 2-3 in that the plurality of shielding repositories212 serve as physical barriers, e.g., insulators, to substantiallyinhibit or prevent thermal radiation Q emitted by the walls 18 a-18 d ofthe lyophilization chamber 16 from reaching the target material 15stored in the plurality of vessels 14. Moreover, the thermal shield 208of the present embodiment of the device 200 can also optionally providea sublimating cooling effect as described above by selection of anappropriate shielding material 119.

While the plurality of repositories 212 of the thermal shield 208 of theembodiment of the device 200 depicted in FIG. 4 have been described asincluding a plurality of tubes, in alternative embodiments, theplurality of repositories 212 could include vials, beakers, or generallyany other structure capable of storing shielding material and insulatingthe vessels 14 in accordance with the principles of the presentdisclosure.

With any of the foregoing devices 100, 200 described herein, a method oflyophilizing the target material 15 can generally be the same. Forexample, before the devices 100, 200 are loaded into the lyophilizationchamber 16, the one or more shielding cavities 110, 210 can be at leastpartially filled with shielding material 119. Additionally, each of thevessels 14 must be at least partially filled with target material 15.With the shielding cavities 110, 210 and vessels 14 filled, the device100, 200 can be loaded into a lyophilization chamber 16 of afreeze-drying machine 12. When the thermal shield 108, 208 of the device100, 200 includes rear and front portions 108 a, 108 b, as describedabove with reference to FIGS. 2 and 2A, the rear portion 108 a is firstloaded onto the support panel 102 in the lyophilization chamber 16.Then, the vessels 14 can be loaded, and finally, the front portion 108 bcan be loaded. Once everything is loaded, the lyophilization process canbe activated to lyophilize the target material 15 stored in the vessels14. While the target material 15 is being lyophilized, it should beappreciated that the thermal shield 108, 208 substantially inhibits orprevents any thermal radiation emitted from the sidewalls 18 a-18 d ofthe lyophilization chamber 16 from reaching the vessels 14, as describedabove.

In some embodiments, the thermal shield 108, 208 can inhibit the thermalradiation from reaching the vessels by serving as a physical barrier,e.g., an insulator, between the vessels 14 and the walls 18 a-18 d ofthe chamber 16. In some embodiments, the thermal shield 108, 208provides a sublimation cooling effect. FIG. 5 in combination with FIGS.6-9 illustrate the results of testing, which has substantiated thebenefits and advantages of the foregoing subject matter.

Specifically, FIG. 5 illustrates a plan view of a test apparatus 300that was set up including a plurality of vessels 14 arranged in an arrayand containing target material 15 to be lyophilized in a lyophilizationchamber such as the lyophilization chamber 16 of the freeze-dryingmachine 12 depicted in FIG. 1, for example. As such, FIG. 5 alsoillustrates the walls 18 a-18 d of the chamber 16. The apparatus 300 isequipped with a plurality of temperature probes T01-T08 disposed withina variety of vessels 14. The first through fourth probes T01-T04 arelocated in vessels 14 at the substantial center of the array of vessels14. The fifth through eighth T05-T05 probes are located in vessels 14 atthe corners of the array of vessels 14.

FIGS. 6 and 8 graphically illustrate the temperatures sensed by thetemperature probes T01-T08 during the cooling step and the drying stepof a test lyophilization process, respectively, wherein the apparatus300 of FIG. 5 was not equipped with a thermal shield 108. Asillustrated, the lines on the graph, each of which is assigned to aparticular temperature probe T01-T08, show non-uniformity in temperatureat the various locations monitored, particularly between the center andthe outside of the array of vessels 14.

FIGS. 7 and 9 graphically illustrate the temperatures sensed by thetemperature probes T01-T08 during the cooling step and the drying stepof a test lyophilization process, respectively, wherein the apparatus300 of FIG. 5 was equipped with a thermal shield 108. As illustrated,the lines on the graph, each of which is assigned to a particular probeT01-T08, follow the same shape and are tightly grouped, showing uniformtemperatures at the various locations monitored. Accordingly, thethermal shields 108 disclosed herein advantageously help maintain auniform temperature distribution amongst the target material 15 storedin the vessels 14 during the lyophilization process.

In view of the foregoing, it should be appreciated that the variousembodiments described herein provide examples of various devices,systems, and methods constructed in accordance with the principles ofthe present disclosure. These embodiments are not meant to be exclusiveembodiments, but rather, any of the embodiments can be modified toinclude any one or more features of any of the other embodiments. Assuch, it should be appreciated that the examples provided herein are notexhaustive and the various features are interchangeable with each other,as well as with features not specifically disclosed but understood by aperson having ordinary skill in the art.

1. A device for supporting at least one vessel containing a targetmaterial to be lyophilized within a chamber of a freeze drying machine,the device comprising: a support panel having a support surface; acentral region defined by the support panel for supporting the at leastone vessel; a perimeter region defined by the support panel andsurrounding the central region; a thermal shield positioned about theperimeter region and extending transverse to the support surface of thesupport panel such that the thermal shield and the support panel definea storage space for accommodating the at least one vessel; and at leastone shielding cavity defined by the thermal shield and containing ashielding material during a lyophilization process, the shieldingmaterial being distinct from the target material, wherein the device isadapted to be removably supported within the chamber of thefreeze-drying machine such that the thermal shield inhibits thermalradiation emitted by chamber walls defining the chamber.
 2. The deviceof claim 1, wherein the thermal shield comprises: an inner wall portionsurrounding the central region; an outer wall portion surrounding theinner wall portion and spaced from the inner wall portion to define theat least one shielding cavity.
 3. The device of claim 2, wherein the atleast one shielding cavity defined between the inner and outer wallportions of the thermal shield comprises an elongated channelsurrounding the central region of the support panel and for containingthe shielding material.
 4. The device of claim 3, further comprising anelongated opening defined by the elongated channel for enabling at leastone component of the shielding material to exhaust from the elongatedchannel during the lyophilization process.
 5. The device of claim 3,further comprising a cap enclosing the elongated channel, the capdefining a plurality of apertures for controlling a rate at which theshielding material exhausts from the channel during the lyophilizationprocess.
 6. The device of claim 1, wherein the thermal shield comprisesa plurality of shielding repositories arranged side-by-side about theperimeter region of the support panel and surrounding the centralregion, wherein each of the plurality of repositories defines ashielding cavity containing the shielding material during thelyophilization process.
 7. The device of claim 6, wherein each of theshielding repositories comprises a tube.
 8. The device of claim 1,further comprising a shielding material disposed in the shieldingcavity.
 9. A system for lyophilizing target material stored within atleast one vessel, the system comprising: a freeze drying machineincluding a chamber having chamber walls; and a device for supporting atleast one vessel containing a target material to be lyophilized, thedevice comprising: a support panel having a support surface, a centralregion defined by the support panel for supporting the at least oneVessel, a perimeter region defined by the support panel and surroundingthe central region, a thermal shield positioned about the perimeterregion and extending transverse to the support surface of the supportpanel such that the thermal shield and the support panel define astorage space for accommodating the at least one vessel, and at leastone shielding cavity defined by the thermal shield and containing ashielding material during a lyophilization process, the shieldingmaterial being distinct from the target material, the device beingremovably supported within the chamber of the freeze-drying machine,wherein the thermal shield of the device substantially inhibits thermalradiation emitted by the chamber walls of the freeze drying machinewhile the target material is being lyophilized, thereby facilitating auniform temperature distribution amongst the target material stored inthe at least one vessel.
 10. A method of lyophilizing a target materialstored in at least one vessel, the method comprising: at least partiallyfilling at least one shielding cavity with a shielding material thatincludes at least one component that is different from at least onecomponent of the target material, the at least one shielding cavityarranged to surround the at least one vessel; loading the at least onevessel and the at least one shielding cavity into a lyophilizationchamber of a freeze drying machine, the lyophilization chamber havingsidewalls and arranged and configured to support the at least one vesseland the at least one shielding cavity; lyophilizing the target materialstored in the at least one vessel; and inhibiting thermal radiationemitted from the sidewalls of the lyophilization chamber from reachingthe at least one vessel, thereby minimizing variations in temperatureamongst the target material stored in the at least one vessel.
 11. Themethod of claim 10, further comprising loading the at least one vesselonto a central region of a support panel.
 12. The method of claim 10,wherein at least partially filling at least one shielding cavity with ashielding material comprises at least partially filling at least oneelongated channel adapted to surround the at least one vessel.
 13. Themethod of claim 10, wherein at least partially filling at least oneshielding cavity with a shielding material comprises at least partiallyfilling a plurality of repositories arranged side-by-side and adapted tosurround the at least one vessel.
 14. The method of claim 10, whereininhibiting the thermal radiation comprises absorbing the thermalradiation at constant temperature with a phase-changing shieldingmaterial.
 15. The method of claim 14, comprising lyophilizing at least aportion of the shielding material stored in the at least one shieldingcavity generally simultaneously with lyophilizing the target materialstored in the at least one vessel.
 16. The system of claim 9, whereinthe thermal shield comprises: an inner wall portion surrounding thecentral region; an outer wall portion surrounding the inner wall portionand spaced from the inner wall portion to define the at least oneshielding cavity.
 17. The system of claim 16, wherein the at least oneshielding cavity defined between the inner and outer wall portions ofthe thermal shield comprises an elongated channel surrounding thecentral region of the support panel and for containing the shieldingmaterial.
 18. The system of claim 17, further comprising an elongatedopening defined by the elongated channel for enabling at least onecomponent of the shielding material to exhaust from the elongatedchannel during the lyophilization process.
 19. The system of claim 17,further comprising a cap enclosing the elongated channel, the capdefining a plurality of apertures for controlling a rate at which theshielding material exhausts from the channel during the lyophilizationprocess.
 20. The system of claim 19, wherein the thermal shieldcomprises a plurality of shielding repositories arranged side-by-sideabout the perimeter region of the support panel and surrounding thecentral region, wherein each of the plurality of repositories defines ashielding cavity containing the shielding material during thelyophilization process.
 21. The system of claim 20, wherein each of theshielding repositories comprises a tube.
 22. The system of claim 9,further comprising a shielding material disposed in the shieldingcavity.